17-21551325-G-A

Position:

• chr17-21551325-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NR_160801.1(LINC02693):​n.354C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000429 in 1,399,008 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000043 (1 hom.)
• Consequence: LINC02693 NR_160801.1 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.229

Genes affected

LINC02693 (HGNC:27904): (long intergenic non-protein coding RNA 2693)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13040832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINC02693	NR_160801.1	n.354C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINC02693	ENST00000654263.1	n.169+21901C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000644 AC: 1 AN: 155382 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 82474

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000406

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000429 AC: 6 AN: 1399008 Hom.: 1 Cov.: 30 AF XY: 0.00000290 AC XY: 2 AN XY: 689982

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000140

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.98C>T (p.T33I) alteration is located in exon 1 (coding exon 1) of the C17orf51 gene. This alteration results from a C to T substitution at nucleotide position 98, causing the threonine (T) at amino acid position 33 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	6.3
DANN	Benign	0.89
DEOGEN2	Benign	0.092	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N;N
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.050
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.89	P
Vest4		0.14
MutPred		0.15		Loss of phosphorylation at T33 (P = 0.0502);
MVP		0.014
ClinPred		0.42	T
GERP RS		0.15
Varity_R		0.072
gMVP		0.092

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1555577028; hg19: chr17-21454588;